The outer surfaces and inner cavities of the body are lined with sheets of contiguous, tightly apposed cells. These cell sheets, called epithelia, comprise the outer layer of the skin and line the gastrointestinal, respiratory, and genital tracts. Epithelial cell sheets form a barrier between the body and its environment and between different body compartments. This barrier impedes the movement of water, solutes, and cells to maintain distinct biochemical and cellular compositions on each side of the barrier. However, molecules can be selectively transported from one side of the barrier to another. For example, epithelial cells lining the gut not only prevent the contents of the gut from invading surrounding tissue but also actively transport nutrients from the gut cavity across the epithelia where they diffuse into blood vessels.
Epithelial cells are columnar, polarized cells. The apical surface of the epithelial cell is exposed to the environment or to a body cavity; the lateral surface adjoins other epithelial cells; and the basal surface contacts the lamina, a supportive layer of extracellular matrix proteins containing collagen, laminin and other proteoglycans. Inside the body, the apical surface of an epithelium is coated with mucous, a viscous extracellular matrix comprised primarily of glycoproteins secreted from specialized cells of the epithelium. Mucous lubricates the underlying epithelium and protects it from physical damage, dehydration, particulate contaminants, and microbial infection. For example, foreign particles inhaled into the respiratory tract are trapped by mucous and eliminated in the sputum. In addition, mucous is the first line of immunological defense against pathogens. Antibodies, especially those of the IgA class, are secreted by immune cells embedded in the lamina and are selectively transported across the epithelium into the mucous. Within the lamina, the epithelial cell, and the mucous, these antibodies encounter and neutralize pathogens such as viruses. (Mazanec, M. B. et al. (1993) Immunol. Today 14:430-435.)
The olfactory neuroepithelium is a highly specialized sensory epithelium that lines the nasal passage. The olfactory neuroepithelium is comprised primarily of two cell types, the olfactory neurons and the sustentacular cells. Olfactory neurons are chemosensory cells. Extending from the apical surface of the olfactory neuron are numerous dendritic cilia. These cilia are elongated sensory structures comprised of radially arranged microtubules surrounded by cytosol and enclosed by plasma membrane. The cilia protrude through the mucous layer to encounter odorant molecules inhaled into the nasal passage. Odorant receptors and their signal transduction machinery are associated with the ciliary plasma membrane. Extending from the basal surface of the olfactory neuron into the lamina are axons that transmit sensory inputs from the olfactory neuron to the brain. Sustentacular cells, or supporting cells, surround the sensory neurons. They do not function in sensation but instead insulate sensory neurons from one another, secrete mucous components from their apical surfaces onto the epithelial surface, and transport molecules through the epithelium. Embedded within the lamina are the Bowman's glands whose ducts project to the epithelial surface. Through these ducts, Bowman's glands secrete mucous components onto the epithelial surface. (Takagi, S. F. (1989) Human Olfaction, University of Tokyo Press, Tokyo, Japan.)
An abundant glycoprotein component of olfactory mucous from the bullfrog Rana catesbeiana has been purified. (Snyder, D. A. et al. (1991) Biochemistry 30:9143-9153.) This glycoprotein, olfactomedin, constitutes up to 5% of the total protein present in olfactory neuroepithelium. Its abundance suggests that it is one of the major structural components of the extracellular mucous matrix. Immunohistochemical studies show that olfactomedin is localized in secretory organelles of Bowman's glands and sustentacular cells and at the mucociliary surface. The cDNA encoding olfactomedin contains a 464-amino acid open reading frame. Prior to its secretion, olfactomedin is glycosylated and the first 16 amino acids are proteolytically removed, generating a glycoprotein of 57 kilodaltons. Intramolecular disulfide bonds are predicted to maintain the protein in a hairpin-like conformation. Intermolecular disulfide bonds form olfactomedin homodimers of about 120 kilodaltons and may possibly form higher-order polymers. Olfactomedin is associated specifically with olfactory neuroepithelium and not with other mucociliary epithelia. The intimate association of olfactory mucous with dendritic cilia suggests that olfactomedin may influence the maintenance, growth, or differentiation of these structures or promote the interactions between odorant molecules and their receptors on the ciliary membrane. (Yokoe, H. and Anholt, R. R. H. (1993) Proc. Natl. Acad. Sci. USA 90:4655-4659.)
Pathological conditions that result from disruption of the olfactory mucosa include chronic infectious rhinitis, influenza infection, atrophic rhinitis, and ozena, a rare form of rhinitis characterized by degeneration of the mucosal epithelium. Increased susceptibility to toxic fumes, for example, those containing heavy metals, can also result. (Takagi, supra.)
The discovery of a new extracellular mucous matrix glycoprotein and the polynucleotides encoding it satisfies a need in the art by providing new compositions which are useful in the diagnosis, treatment, and prevention of infections, gastrointestinal disorders, and cancer.